The gene genius

Worried about GM food? You can thank Gregor Mendel. David Bodanis tells the story of the science behind the news and the people who pioneered it.

enetic science is never out of the headlines these days, what with the controversy over genetically modified food, the human genome project, and scientists claiming they have found the specific genes that hold the key to terrible diseases.

Odd, then, that the father of genetics, Gregor Mendel, is as neglected today as he was in his lifetime.

Born in 1822 in Moravia in what is now the Czech Republic, Mendel had wanted to be a schoolteacher, but couldn't afford more than a few terms at university. He became a monk instead, but didn't give up his science. In 1866, he sent an account of some research he had been conducting to many of the leading biologists in Europe, including the well-known Professor Kerner in Innsbruck, Austria. Mendel must have had high hopes that one of these distinguished scientists would recognise the value of his work - but he was to be disappointed.

Like many great scientific discoverers, Mendel was trying to find an explanation for something most people took for granted. Everyone knows that children take after their parents, at least a little bit. If your parents have dark hair, you're more than likely to have dark hair. If they're tall, then you too are likely to end up a little taller than average. What's curious is that children are never an exact average of what their parents are like. If a father is 6ft tall and a mother is 5ft, it's very rare for all the children to be exactly 5ft 6in. Similarly, if one parent has blonde hair and the other has black hair, sometimes the children will have hair that's halfway in-between in colour, but pretty often they'll divide up: some will have black hair, some will have blonde - or maybe one child will even end up with red hair.

Mendel wanted to know how this could happen. He formed the idea that plants and animals don't have copies of themselves inside, as some researchers had earlier thought. Rather, our body's cells are built from blueprints that contain much of the information on how to construct us. It was an important distinction, and Mendel was one of the first to think of it.

Our body's blueprints can be separated into constituent fragments, and it is those fragments that combine in the next generation. If a child inherits the blueprint that operates the construction of black hair, it doesn't matter if the other parent is blonde, because black-hair instruction (the dominant gene) is stronger than blonde-hair (the recessive gene).

Genetic control is so powerful, in fact, that every person on earth also gets a distinct set of fingerprints. If you look at your own fingerprints and those of a friend, it will seem that the swirls are almost identical, but if you carefully sketch them out you will see that they really are different.

The way Mendel proved his blueprint theory was a brilliant example of decisive science experimentation, but pretty disastrous for his own career. In his experiment, he crossed yellow peas with green peas. The first generation of descendants were all yellow, but the second generation, he found, had some peas which were yellow and some which were green! He had shown that the instructions for creating green peas had "survived" intact, deep inside the first generation of yellow pea plants. Plants can carry such "sleeper" instructions. Our genetic inheritance is built up of blueprint fragments: some of them are used, while others just wait.

It was one of the prime discoveries of the 19th century, but most biologists Mendel sent his paper to just thought he was talking about peas! They didn't realise the possible significance for humans - the fact that Mendel's experiments had illuminated the operation of recessive and dominant genes, the mechanism that controls the development of humans and trees and dolphins, just as much as it does peas. The whole science of genetics springs from this principle, but there were no accolades for Gregor Mendel. Professor Kerner's papers were examined after his death. The article Mendel sent had never been opened.

* DNA

Mendel's work was rediscovered around 1900, and it gradually led to a better understanding of these inherited "blueprints" we carry within our bodies.

The first part of the task was accomplished in 1953, through the work of the American James Watson, and the Briton Francis Crick, working at Cambridge University. They described a molecule called DNA, short for deoxyribonucleic acid. This carries the miniaturised blueprints Mendel had foreseen all those decades before. Watson and Crick were awarded a Nobel Prize for their work. Each DNA molecule looks like a long, twisted ladder, the famous "double helix" shape. The outsides of the ladder were built out of sugars, but the inside - the rungs you'd have to step on to walk up the ladder - were made from short, stubby chemicals that could be ripped in half, like Velcro.

This is where the blueprints are found. A gene is simply a stretch of DNA that carries enough of these rungs to provide a useful chunk of information. Each DNA molecule is long, and has many thousands of genes on it.

In the years since Watson and Crick published their first model of DNA, a lot more detail has been learned about how the DNA blueprint machine operates.

The most surprising thing is that one gene does not control one surface trait. There's no single gene for how moody we are, or for intelligence, or for sporting ability. Each of those traits results from a mixture of several quite different operations. A great sprinter, for example, needs genes that are sufficient for accumulating calcium (for strong bones), and genes that influence the time at which leg growth stops (so the calcium is accumulated for longer than average, thus leading to long leg bones), and genes that ensure a good amount of fast-twitch muscle fibres in the whole body.

Even more, genes don't work in a void. Identical twins, like the girls on our cover this month, arise when a fertilised egg splits in two. These twins have identical genes. But this doesn't mean that the two individuals will necessarily end up as adults with the same looks or personalities.

If, for example, the identical twin brother or sister of an Olympic champion had been raised in a setting where there wasn't enough good quality food, the genes "waiting" to operate the bone and muscle building would never have been able to get started.

The Human Genome Project is often misunderstood for this reason. It is an arrangement by a number of universities and labs worldwide to work out the chemical details of every rung of every gene in human DNA.

It is a worthy endeavour if one expects to find out aspects of how various diseases operate, and to provide the raw material for generations of researchers to use in understanding how our genetic instructions interact. But it won't allow us to find "the" gene for any given trait. Aside from a few trivial characteristics, no such thing exists.

Another surprise was that the genes themselves are of different sorts. Some give direct instructions for building a chemical. Others are more like foremen - instead of working themselves, they boss the first sort of genes about. A number of these controller genes act like accelerators, and speed up the action of the "worker" genes they control. Others act like brakes. Under normal circumstances, the accelerators and brakes adjust their settings as the body's needs change. If someone drinks alcohol, for example, then accelerator genes in the DNA blueprint start operating, producing dehydrogenase, which helps break the alcohol down. Similarly, if someone runs, appropriate "accelerator" genes register the exercise, and build up the necessary chemicals to handle it - which we register as growing muscle.

Sometimes, though, the accelerators get stuck in the "on" position. In some circumstances, that seems to be the way a cancer might start: a cell divides and nourishes uncontrollably, and the DNA blueprint gushes out even more of the chemical causing it to happen. We're usually safe from such flaws because the DNA that contains our genes is so important a molecule that it has developed the ability to repair itself. There are genes whose sole job is to produce repair chemicals, which skim along the DNA strand, mending all flaws as they go.

The latest and most controversial development in the science Mendel pioneered is the ability to manipulate genes. In genetically modified (GM) crops, chunks of genes for, say, resistance to a pesticide can be extracted from one species and inserted into the DNA of another.

Genetic modification could make it possible to produce maize that can withstand drought (thus easing the livelihood of impoverished growers in the developing world) or rice that delivers a dose of vitamin A (thus potentially eliminating deficiency-induced blindness). Its opponents say that to transfer genetic material between species could inadvertently produce monstrous new hybrids with unforeseen and destructive potential: weeds resistant to all pesticides, for example.

However this technology comes to be used - and it's a political issue as much as a scientific one - it shows the tremendous consequences flowing from the work of the neglected Gregor Mendel.

WHAT MENDAL DID

When Mendel crossed seemingly "pure" yellow peas with seemingly "pure" green peas he found that the first generation produced only yellow peas, but the self-fertilised second generation produced a mix. There were 6,022 yellow and 2,001 green peas in that generation. The ratio is almost exactly 3:1.

Similar experiments with other traits of peas - such as flower colour, or stem height - led him to conclude that what was happening could be represented by the equivalent of the diagram, right. He imagined that there was one "factor" within the pea cells which led to the appearance of a yellow pea - call that Y - and a second factor, which, if it ever occurred entirely on its own, would lead to the appearance of a green pea, but which if it occurred with a "Y" factor would end up being "masked". Call that second factor "g". (These two factors are what we would today call a dominant and a recessive gene.) Only the bottom right-hand corner of the second generation gets a "gg" mix. That's only one out of the four possible boxes in that generation. Since the three other possibilities will have either one or two "Y" factors - and either of those would be enough to produce the surface appearance of pure yellow - Mendel concluded his reasoning was right.

CURRICULUM LINKS

At key stage 2, children learning science will begin to "make links between ideas and to explain things using simple models and theories". They should be taught that science is "about thinking creatively to explain how living (and non-living) things work", and that "it is important to test ideas using evidence from observation and measurement". The story of Gregor Mendel is an excellent example of this, showing how patient observation and measurement over a long period of time confirmed a scientific theory.

Activities Any investigation involving plants is likely to be long-term; but classroom plants of the same species and different in other ways - for example, red and white flowers - could be cross-fertilised using a soft paintbrush to transfer pollen. If you collect the seeds, plant and grow them, the results should be a mix of colours, and not pink.

Siblings in school with the same biological parents will show the differences in one generation. If you have identical twins in school, you might ask them if they are willing to be involved in a sensitive look at the differences and similarities between them. If you have non-identical twins, they offer further proof of the difference between offspring from the same biological parents.

NB: Any study of heredity brings the possibility that children can make inappropriate discoveries about their biological parents. Avoid being definite about hereditary rules to do with characteristics such as eye or hair colour.

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